The long-term objective of this study is to explain the mechanism of insulin action in the human body in order to contribute towards improvement of clinical treatment of diabetes. The specific aim of the proposed study is to elucidate the mechanism by which the interaction of insulin with its cellular receptor leads to the stimulation of phosphodiesterase. This year, we will focus our attention to the insulin-dependent physical change in the phosphodiesterase molecule. Last year, we found that the apparent molecular size of the enzyme is increased by insulin. This may be caused by the binding of unknown protein, by the change in the molecular conformation, or by the increase in the combined detergent. It is hoped that this line of study will provide a clue on the possible mechanism of insulin action.